Clinical features and genetic variations of severe neonatal hyperbilirubinemia:Five case reports

BACKGROUND Neonatal hyperbilirubinemia is a common problem faced by pediatricians.The role of genetic factors in neonatal jaundice has been gradually recognized.This study aims to identify genetic variants that influence the bilirubin level in five patients using next-generation sequencing(NGS).CASE SUMMARY Five neonates with severe hyperbilirubinemia were retrospectively studied.They exhibited bilirubin encephalopathy,hypothyroidism,ABO blood type incompatibility hemolysis,glucose-6-phosphate dehydrogenase(G6PD)deficiency and premature birth,respectively.A customized 22-gene panel was designed,and NGS was carried out for these neonates.Eight variations(G6PD c.G1388A,HBA2 c.C369G,ABCC2 c.C3825G,UGT1A1 c.G211A,SPTB c.A1729G,EPB41 c.G520A,c.1213-4T>G and c.A1474G)were identified in these five neonates.Genetic mutations of these genes are associated with G6PD deficiency,thalassemia,Dubin-Johnson syndrome,Gilbert syndrome,hereditary spherocytosis,and hereditary elliptocytosis.One of the neonates was found to have compound variants of the EPB41 splice site c.1213-4T>G and c.G520A(p.E174K),but no elliptocyte was seen on his blood smear of 4 years old.CONCLUSION Pathological factors of severe neonatal hyperbilirubinemia are complicated.Genetic variants may play an important role in an increased risk of neonatal hyperbilirubinemia,and severe jaundice in neonates may be related to a cumulative effect of genetic variants.

Minimum Time Overtaking Problem of Vehicle Handling Inverse Dynamics Based on Two Kinds of Safe Distances

Overtaking accidents caused by improper operations performed by a driver occur frequently. However, most stud?ies on overtaking safety have neglected research into driver control input. A novel method is proposed to obtain the driver control input during the overtaking process. Meanwhile, to improve the safety of overtaking, two types of safe distances, and the time of the overtaking are considered. Path constraints are established when considering the two types of safe distances. An optimal control model is established to solve the minimum time maneuver under multiple constraints. Using the Gauss pseudospectral method, the optimal control problem is converted into a nonlinear pro?gramming problem, which is then solved through sequential quadratic programming(SQP). In addition, the e ective?ness of the proposed method is verified based on the results of a Carsim simulation. The simulation results show that by adopting an inverse dynamics method to solve the manipulation problem of the vehicle’s minimum overtaking time, the manipulation capability of a vehicle in completing an overtaking safely within the minimum time can be obtained. This method can provide a reference for research into the active safety of manned and unmanned vehicles.

Numerical Prediction of Ride Comfort of Tracked Vehicle Equipped with Novel Flexible Road Wheels

Enhancing ride comfort has always constituted a crucial focus in the design and research of modern tracked vehicles,heavily reliant on the driving system's performance.While the road wheel is a key component of the driving system,traditional road wheels predominantly adopt a solid structure,exhibiting subpar adhesion performance and damping effects,thereby falling short of meeting the demands for high-speed,stable,and long-distance driving in tracked vehicles.Addressing this issue,this paper proposes a novel type of flexible road wheel(FRW)characterized by a catenary construction.The study investigates the ride comfort of tracked vehicles equipped with flexible road wheels by integrating finite element and vehicle dynamic.First,three-dimensional(3D)finite element(FE)models of both flexible and rigid road wheels are established,considering material and contact nonlinearities.These models are validated through a wheel radial loading test.Based on the validated FE model,the paper uncovers the relationship between load and radial deformation of the road wheel,forming the basis for a nonlinear mathematical model.Subsequently,a half-car model of a tracked vehicle with seven degrees of freedom is established using Newton's second law.A random road model,considering the track effect and employing white noise,is constructed.The study concludes by examining the ride comfort of tracked vehicles equipped with flexible and rigid road wheels under various speeds and road grades.The results demonstrate that,in comparison to the rigid road wheel(RRW),the flexible road wheel enhances the ride comfort of tracked vehicles on randomly uneven roads.This research provides a theoretical foundation for the implementation of flexible road wheels in tracked vehicles.

High-Performance and Large-Area Inverted Perovskite Solar Cells Based on NiO_(x) Films Enabled with A Novel Microstructure-Control Technology

The improvement in the efficiency of inverted perovskite solar cells(PSCs)is significantly limited by undesirable contact at the NiO_(x)/perovskite interface.In this study,a novel microstructure-control technology is proposed for fabrication of porous NiO_(x)films using Pluronic P123 as the structure-directing agent and acetylacetone(AcAc)as the coordination agent.The synthesized porous NiO_(x)films enhanced the hole extraction efficiency and reduced recombination defects at the NiO_(x)/perovskite interface.Consequently,without any modification,the power conversion efficiency(PCE)of the PSC with MAPbl_(3)as the absorber layer improved from 16.50%to 19.08%.Moreover,the PCE of the device composed of perovskite Cs0.05(MA_(0.15)FA_(0.85))_(0.95)Pb(I_(0.85)Br_(0.15))_(3)improved from 17.49%to 21.42%.Furthermore,the application of the fabricated porous NiO_(x)on fluorine-doped tin oxide(FTO)substrates enabled the fabrication of large-area PSCs(1.2 cm^(2))with a PCE of 19.63%.This study provides a novel strategy for improving the contact at the NiO_(x)/perovskite interface for the fabrication of high-performance large-area perovskite solar cells.

Trajectory Tracking of Autonomous Vehicle with the Fusion of DYC and Longitudinal–Lateral Control

The current research of autonomous vehicle motion control mainly focuses on trajectory tracking and velocity tracking. However, numerous studies deal with trajectory tracking and velocity tracking separately, and the yaw stability is seldom considered during trajectory tracking. In this research, a combination of the longitudinal–lateral control method with the yaw stability in the trajectory tracking for autonomous vehicles is studied. Based on the vehicle dynamics, considering the longitudinal and lateral motion of the vehicle, the velocity tracking and trajectory tracking problems can be attributed to the longitudinal and lateral control. A sliding mode variable structure control method is used in the longitudinal control. The total driving force is obtained from the velocity error in order to carry out velocity tracking. A linear time-varying model predictive control method is used in the lateral control to predict the required front wheel angle for trajectory tracking. Furthermore, a combined control framework is established to control the longitudinal and lateral motions and improve the reliability of the longitudinal and lateral direction control. On this basis, the driving force of a tire is allocated reasonably by using the direct yaw moment control, which ensures good yaw stability of the vehicle when tracking the trajectory. Simulation results indicate that the proposed control strategy is good in tracking the reference velocity and trajectory and improves the performance of the stability of the vehicle.

Estimation of Road Friction Coefficient in Different Road Conditions Based on Vehicle Braking Dynamics

The accurate estimation of road friction coeffi- cient in the active safety control system has become increasingly prominent. Most previous studies on road friction estimation have only used vehicle longitudinal or lateral dynamics and often ignored the load transfer, which tends to cause inaccurate of the actual road friction coef- ficient. A novel method considering load transfer of front and rear axles is proposed to estimate road friction coef- ficient based on braking dynamic model of two-wheeled vehicle. Sliding mode control technique is used to build the ideal braking torque controller, which control target is to control the actual wheel slip ratio of front and rear wheels tracking the ideal wheel slip ratio. In order to eliminate the chattering problem of the sliding mode controller, integral switching surface is used to design the sliding mode sur- face. A second order linear extended state observer is designed to observe road friction coefficient based on wheel speed and braking torque of front and rear wheels. The proposed road friction coefficient estimation schemes are evaluated by simulation in ADAMS/Car. The results show that the estimated values can well agree with the actual values in different road conditions. The observer can estimate road friction coefficient exactly in real-time andresist external disturbance. The proposed research provides a novel method to estimate road friction coefficient with strong robustness and more accurate.

妊娠糖尿病患者血清脂联素表达及与炎症因子、胰岛素抵抗关系

目的:探讨血清脂联素(APN)在妊娠糖尿病患者中的表达特征及其与炎症因子、胰岛素抵抗的关系。方法:选取118例孕妇和50例非妊娠妇女,分别纳入观察组与对照组。观察组孕妇根据糖耐量测试结果分为糖尿病组(50例)与非糖尿病组(68例)。对所有研究对象进行血清APN、肿瘤坏死因子α(INF-α)、白介素-6(IL-6)、超敏C-反应蛋白(hs-CRP)、空腹胰岛素(FINS)、甘油三酯(TG)、胰岛素抵抗指数(HOMA-IR)水平。对比并分析血清APN与炎症因子及HOMA-IR的关系。结果:观察组hs-CRP、IL-6、TG、HOMA-IR、TNF-α水平均高于对照组,APN水平低于对照组(P<0.05)。妊娠糖尿病组的hs-CRP、IL-6、HOMA-IR、TNF-α水平均高于妊娠非糖尿病组,APN水平低于妊娠非糖尿病组(均P<0.05),两组TG水平比较无差异(P>0.05)。spearman相关分析结果显示,APN与IL-6、hs-CRP、TNF-α、HOMA-IR均呈负相关(P<0.05)。结论:妊娠糖尿病孕妇的血清APN表达下调,可造成炎症反应失衡,引起胰岛素抵抗,其与炎症因子、胰岛素抵抗存在着负相关关系。

Etiology analysis for term newborns with severe hyperbilirubinemia in eastern Guangdong of China

BACKGROUND Neonatal hyperbilirubinemia is one of the common diseases of newborns that typically presents with yellow staining of skin,resulting in sequelaes such as hearing loss,motor and intellectual development disorders,and even death.The pathogenic factors of neonatal hyperbilirubinemia are complex.Different cases of hyperbilirubinemia may have a single or mixed etiology.AIM To explore the etiological characteristics of severe hyperbilirubinemia in term newborns of eastern Guangdong of China.METHODS Term newborns with severe hyperbilirubinemia in one hospital from January 2012 to December 2021 were retrospectively analyzed.The etiology was determined according to the laboratory results and clinical manifestations.RESULTS Among 1602 term newborns with hyperbilirubinemia in eastern Guangdong of China,32.20%(580/1602)was severe hyperbilirubinemia.Among the causes of severe hyperbilirubinemia,neonatal hemolysis accounted for 15.17%,breast milk jaundice accounted for 12.09%,infection accounted for 10.17%,glucose-6-phosphate dehydrogenase(G6PD)deficiency accounted for 9.14%,and the coexistence of multiple etiologies accounted for 6.55%,unknown etiology accounted for 41.72%.ABO hemolysis and G6PD deficiency were the most common causes in the 20 cases with bilirubin encephalopathy.94 severe hyperbilirubinemia newborns were tested for uridine diphosphate glucuronosyl transferase 1A1(UGT1A1)*6 variant(rs4148323,c.211G>A,p.Arg71Gly),9 cases were 211 G to A homozygous variant,37 cases were 211 G to A heterozygous variant,and 48 cases were wild genotypes.CONCLUSION The main cause for severe hyperbilirubinemia and bilirubin encephalopathy in eastern Guangdong of China were the hemolytic disease of the newborns,G6PD deficiency and infection.UGT1A1 gene variant was also a high-risk factor for neonatal hyperbilirubinemia.Targeted prevention and treatment according to the etiology may reduce the occurrence of bilirubin encephalopathy and kernicterus.

Influence Analysis of Machining and Installation Errors on the Radial Stiffness of a Non-Pneumatic Mechanical Elastic Wheel

Machining and installation errors are unavoidable in mechanical structures. However, the effect of errors on radial stiffness of the mechanical elastic wheel(ME-Wheel) is not considered in previous studies. To this end, the interval mathematical model and interval finite element model of the ME-Wheel were both established and compared with bench test results. The intercomparison of the influence of the machining and installation errors on the ME-Wheel radial stiffness revealed good consistency among the interval mathematical analysis, interval finite element simulation,and bench test results. Within the interval range of the ME-Wheel machining and installation errors, parametric analysis of the combined elastic rings was performed at different initial radial rigidity values. The results showed that the initial radial stiffness of the flexible tire body significantly influenced the ME-Wheel radial stiffness, and the inverse relationship between the hinge unit length or suspension hub and the radial stiffness was nonlinear. The radial stiffness of the ME-Wheel is predicted by using the interval algorithm for the first time, and the regularity of the radial stiffness between the error and the load on the ME-Wheel is studied, which will lay the foundation for the exact study of the ME-Wheel dynamic characteristics in the future.

Influence of structure and material on the vibration modal characteristics of novel combined flexible road wheel

Aiming at the independent development of tracked vehicles,it is urgent to improve its mobility,passability and ride comfort,a new type of flexible road wheel with a“wheel-hinge-hub”combined structure is proposed in this study.The vibration model characteristics of the flexible road wheel were studied by the combination of numerical simulation and experiments.The superelasticity of rubber is obtained through uniaxial tensile experiment of the material and a detail three-dimensional nolinear finite element model of the flexible road wheel is established through finite element software ABAQUS.The free vibration equation of the flexible road wheel is solved by Lanczos vector direct superposition method,and its predicted modes and natural frequencies are compared with experimental results,which verifies the accuracy and reliability of the established finite element model.On this basis,the effects of various key structural or material factors on the natural frequencies of the flexible road wheel are studied using orthogonal experimental design method.Besides,the vibration modal characteristics of the flexible road wheel are also compared with those of the rigid road wheel.The research results provide a theoretical basis for the vibration and noise reduction of flexible road wheel.

Thermally Evaporated ZnSe for Efficient and Stable Regular/Inverted Perovskite Solar Cells by Enhanced Electron Extraction

Electron transport layers(ETLs)are crucial for achieving efficient and stable planar perovskite solar cells(PSCs).Reports on versatile inorganic ETLs using a simple film fabrication method and applicability for both low-cost planar regular and inverted PSCs with excellent efficiencies(>22%)and high stability are very limited.Herein,we employ a novel inorganic ZnSe as ETL for both regular and inverted PSCs to improve the efficiency and stability using a simple thermal evaporation method.The TiO_(2)-ZnSe-FAPbl_(3)heterojunction could be formed,resulting in an improved charge collection and a decreased carrier recombination further proved through theoretical calculations.The optimized regular PSCs based on TiO_(2)/ZnSe have achieved 23.25%efficiency with negligible hysteresis.In addition,the ZnSe ETL can also effectively replace the unstable bathocuproine(BCP)in inverted PSCs.Consequently,the ZnSe-based inverted device realizes a champion efficiency of 22.54%.Moreover,the regular device comprising the TiO_(2)/ZnSe layers retains 92%of its initial PCE after 10:00 h under 1 Sun continuous illumination and the inverted device comprising the C_(60)/ZnSe layers maintains over 85%of its initial PCE at 85℃for 10:00 h.This highlights one of the best results among universal ETLs in both regular and inverted perovskite photovoltaics.

Application of an amphipathic molecule at the NiO_(x)/perovskite interface for improving the efficiency and long-term stability of the inverted perovskite solar cells

The presence of defects and detrimental reactions at NiO_(x)/perovskite interface extremely limit the efficiency performance and long-term stability of the perovskite solar cells(PSCs) based on NiO_(x).Herein,an amphipathic molecule Triton X100(Triton) is modified on the NiO_(x)surface.The hydrophilic chain of Triton as a Lewis base additive can coordinate with the Ni3+on the NiO_(x)surface which can passivate the interfacial defects and hinder the detrimental reactions at the NiO_(x)/perovskite interface.Additionally,the hydrophobic chain of Triton protrudes from the NiO_(x)surface to prevent moisture from penetrating into the NiO_(x)/perovskite interface.Consequently,the NiO_(x)/Triton-based devices(MAPbI3as absorbing layer) show superior moisture and thermal stability,retaining 88.4% and 64.3% of the initial power conversion efficiency after storage in air(40%-50% relative humidity(RH)) at 25 ℃ for 1070 h and in N2at 85℃ for 800 h,respectively.Moreover,the efficiency increases from 17.59% to 19.89% because of the passivation defect and enhanced hole-extraction capability.Besides,the NiO_(x)/Triton-based PSCs with Cs_(0.05)(MA_(0.15)FA_(0.85))_(0.95)Pb(I_(0.85)Br_(0.15))3perovskite as the light-absorbing layer also exhibits better moisture and thermal stability compared to the control devices,indicating the viability of our strategies.Of particular note,a champion PCE of 22.35% and 20.46% was achieved for small-area(0.1 cm^(2)) and large-area(1.2 cm^(2)) NiO_(x)/Triton-based devices,respectively.

Preliminary study on Anti-inflammatory and Anti-tumor Effects of Gelatin-based on pH-responsive Drugloaded Nanoparticles

Gelatin as one kind of nano-drug carrier is a polysaccharide which can be absorbed after releasing all nano-drugs.Poly(ethylene glycol)as a polymer material that can modify nano-drugs is able to extend circulatory time of doxorubicin and aspirin,enhance stability and reduce toxicity.At precancerous,aspirin will be released slowly to resist inflammation.When tumor cell appears at a more advance stage,doxorubicin release from Gel to achieve anti-tumor effect.After all those steps,poly(ethylene glycol)could be expelled from body.In brief,the nano-drug that has doxorubicin and aspirin is able to prevent the growth of tumor cells and kill them when they appear more precisely.

Structural modulation and assembling of metal halide perovskites for solar cells and light-emitting diodes

Metal halide perovskites possess appealing optoelectronic properties and have been widely applied for solar energy harvesting and light emitting.Although perovskite solar cells(PeSCs)and perovskite light-emitting diodes(PeLEDs)have been developed rapidly in recent years,there are still no universal rules for the selection of perovskites to achieve high-performance optoelectronic devices.In this review,the working mechanisms of PeSCs and PeLEDs are first demonstrated with the discussion on the factors which determine the device performance.We then examine the optoelectronic properties of perovskites with structures modulated from 3D,2D,1D to 0D,and analyze the corresponding structure-property relationships in terms of photo-electric and electric-photo conversion processes.Based on the unique optoelectronic properties of structurally modulated perovskites,we put forward the concept of structural assembling engineering that integrate the merits of different types of perovskites within one matrix and elaborate their excellent properties for applications of both PeSCs and PeLEDs.Finally,we discuss the potential challenges and provide our perspectives on the structural assembling engineering of perovskites for future optoelectronic applications.

High-power bifacial perovskite solar cells with shelf life of over 2000h

The world-record power conversion efficiency(PCE)of organometallic perovskite solar cells(PSCs)has rapidly increased to 25.2% within ten years due to the superb optoelectronic properties of the organometallic perovskite materials[1-4].However,the long-term stability issue remains a key obstacle for the commercialization of PSCs[5].There are several extrinsic and intrinsic factors known to directly influence the stability of PSCs.Extrinsic factors such as moisture and oxygen in the air can accelerate the degradation of PSCs,but such factors can be effectively eliminated by advanced encapsulation technologies[6,7].

Bayesian dual neural networks for recommendation

Most traditional collaborative filtering(CF)methods only use the user-item rating matrix to make recommendations,which usually suffer from cold-start and sparsity problems.To address these problems,on the one hand,some CF methods are proposed to incorporate auxiliary information such as user/item profiles;on the other hand,deep neural networks,which have powerful ability in learning effective representations,have achieved great success in recommender systems.However,these neural network based recommendation methods rarely consider the uncertainty of weights in the network and only obtain point estimates of the weights.Therefore,they maybe lack of calibrated probabilistic predictions and make overly confident decisions.To this end,we propose a new Bayesian dual neural network framework,named BDNet,to incorporate auxiliary information for recommendation.Specifically,we design two neural networks,one is to learn a common low dimensional space for users and items from the rating matrix,and another one is to project the attributes of users and items into another shared latent space.After that,the outputs of these two neural networks are combined to produce the final prediction.Furthermore,we introduce the uncertainty to all weights which are represented by probability distributions in our neural networks to make calibrated probabilistic predictions.Extensive experiments on real-world data sets are conducted to demonstrate the superiority of our model over various kinds of competitors.

Metformin targets liver tumor-initiating cells through the PI3K/Akt/mTOR survival pathway

Liver tumor-initiating cells(T-ICs) are thought to be inherently resistant to the cytotoxic effects of chemotherapy, and can self-renewal and maintain tumor-initiating potential. Therefore, effective anticancer research strategies should target the unique properties of T-ICs. In this study, we found that metformin, a first-line drug of choice for the treatment of type 2 diabetes, inhibited liver T-ICs both in vivo and in vitro. Metformin inhibited the formation of hepatospheres and epithelial-specific antigen-positive(ESA,CD133?) cell colonies by hepatocellular carcinoma(HCC)cell lines. Metformin also downregulated the expression of several T-IC-related genes which are involved in the signaling pathways, governing the self-renewal, proliferation and differentiation of T-ICs. Furthermore, the targeting of liver T-ICs by metformin was PI-3-kinase-Akt-mTOR(PI3K/Akt/mTOR)-pathway dependent. The PI3K/Akt/mTOR inhibitor LY294002 and rapamycin abolished the inhibitory effect of metformin on CD133?cells, and the PI3K/Akt/mTOR stimulator EGF promoted the inhibitory effect of metformin on CD133?cells. Metformin also dramatically decreased the tumor volume and number of CD133 expressing tumor cells in a xenograft mouse model. Metformin exerted a synergistic effect with cisplatin to target both T-ICs and non-T-ICs, and resulted in the smallest tumor volume and lowest number of CD133 expressing tumor cells. This study indicates that the antidiabetic drug metformin could potentially be used in combination therapy with chemotherapeutic agents to improve the treatment of liver cancer.

Embedding physics domain knowledge into a Bayesian network enables layer-by-layer process innovation for photovoltaics

Process optimization of photovoltaic devices is a time-intensive,trial-and-error endeavor,which lacks full transparency of the underlying physics and relies on user-imposed constraints that may or may not lead to a global optimum.Herein,we demonstrate that embedding physics domain knowledge into a Bayesian network enables an optimization approach for gallium arsenide(GaAs)solar cells that identifies the root cause(s)of underperformance with layer-by-layer resolution and reveals alternative optimal process windows beyond traditional black-box optimization.Our Bayesian network approach links a key GaAs process variable(growth temperature)to material descriptors(bulk and interface properties,e.g.,bulk lifetime,doping,and surface recombination)and device performance parameters(e.g.,cell efficiency).For this purpose,we combine a Bayesian inference framework with a neural network surrogate device-physics model that is 100×faster than numerical solvers.With the trained surrogate model and only a small number of experimental samples,our approach reduces significantly the time-consuming intervention and characterization required by the experimentalist.As a demonstration of our method,in only five metal organic chemical vapor depositions,we identify a superior growth temperature profile for the window,bulk,and back surface field layer of a GaAs solar cell,without any secondary measurements,and demonstrate a 6.5%relative AM1.5G efficiency improvement above traditional grid search methods.

Author Correction:Embedding physics domain knowledge into a Bayesian network enables layer-by-layer process innovation for photovoltaics

In the original version of the published Article,there was ambiguity in Eq.(1).To improve clarity,Eq.(1)has been corrected to the following.